Erythromycin Series. III*. Acylation of Erythromycin Oxime and 9-Amino-3-0-cladinosyl-5-0-desosaminyl-6,11,12-trihydro~y-2,4, 6,8,10,12-hexamethylpentadecane-13-olide with Chlorides of Some Alyphatic Monocarboxylic Acids

In our previous publication1 the preparation of mono- and bis-acyl compounds derived from erythromycin oxime and 9-amino-3-0-cladinosyl-5-0- desosaminyl-6,11,12-trihydroxy-2,4,6,8,10,12-hexamethylpentadecane - 13 - olide (erythromycyl amine) and methyl resp. ethyl ester chlorides of succinic and adipic acid was described. It was found that neither monoacylation nor diacylation effected a substantial change in the antibiotic activity of the starting compounds. The sole exception were ethyl succinates and adipates where a lower activity was found. This is in complete agreement with the relative antibiotic activity of erythromycin and its corresponding esters (methylor ethylsuccinate resp. adipate)

Note on the Preparation of Some Thiobarbiturates

It has been shown that barbituric acid derivatives can be prepared in good yield by gradually adding sodium methoxide as condensation catalyst to a cyanoacetic or malonic ester reacting with urea or its derivatives. The principle of the gradual addition of sodium methoxide as condensing agent has now been extended to condensations of some substituted cyanoacetic and malonic esters with thiourea

Bromination of Tetracycline

Tetracycline (I) reacts with bromine in the presence of pyridine to form lla-bromotetracycline-6,12-hemiketal (II). Dehydration of II, preferably in a mixture of .sulfuric acid and acetonitrile, yields lla-bromo-6-methylenetetracycline (III) as sulfate, which affords 6-methylenetetracycHne (VI) upon reduction. Evidence to support the structures of these products comes from elementary analysis, UV, IR and NMR data

Preparation of Some lmino- and Cyano-imino-substituted Barbiturates

A number of imino- and cyano-iminobarbituric acid derivatives has been prepared in good yield by gradually adding sodium methoxide - as condensation catalyst - to some substituted cyanoacetic and malonic esters reacting with urea, dicyandiamide and guanidine

Synthesen in der Pyrrolizidin- und Indolizidin-Reihe

Ausgehend von 4-(Tetrahydro-2-furyl)-buttersaure (I) und 5-(Tetrahydro-2-furyl)-va~eriansaure (V) werden durch Bromierung mit Brom und rotem Phosphor und ausschlissender Behandlung mit Methanol 2-Brom-(tetrahydro-2-furyl)-saureester als ein Gemisch von bromhaltigen Stoffen erhalten. Die so gewonnenen Bromsaure ester werden mittels Bromwasserstoff in die entsprechenden Tribromester II und VI ilberfilhrt welche dann durch Erhitzen mit methylalkoholischem Ammoniak Pyrrolizidin-3-carborisauremethylester (III) und Indolizidin-5-carbonsauremethylester (VII) lieferten. Durch Reduktion des Esters III und VII mit Lithiumaluminiumhydrid wurden aus III 3-0xymethylpyrrolizidin und aus VII 5-0xymethyl-indolizidin erhalten

Zur Darstellung der 4-(Pyrrolidyl-2)-buttersaure, der 5-(Pyrrolidyl-2)-valeriansaure und des 1-Aza-bicyclo-[0,3,5]decans

Ausgehend von 4-(Tetrahydro-2-furyl)-buttersaureathylester (I) und 5-(Tetrahydro-2-furyl)-valeriansaureathylester (II) werden durch Aufsprengung des Tetrahydrofuranrings mit Bromwasserstoff die entsprechenden Dibromester (II, V) erhalten. Durch nachfolgendes Erhitzen mit methylalkoholischem Ammoniak werden 4-(Pyrrolidyl-2)-buttersaure und 5-(Pyrrolidyl-2)-valeriansaure als Ester (III, VI) dargestellt. Ferner wird eine neue Synthese des 1-Aza-bicyclo-[O, 3, 5]-decans (VIII) beschrieben

Erythromycin Series. II. Acylation of Erythromycin oxime and 9-Amino-3-0-cladinosyl-5-0-desosaminyl-6,11,12-trihydroxy- 2,4,6,8,10,12-hexamethylpentadecane-13-olide with Ester-chlorides of Dicarboxylic Acids

The acylation of erythromycin oxime and 9-amino-3-0-cladinosyl- 5-0-desosaminyl-6,11,12 - trihydroxy-2,4,6,8,10,1 2 - hexamethylpentadecane- 13-olide (erythromycyl amine) was performed by means of dicarboxylic acid chloride esters and the corresponding 0- and N-acyl derivati ves were obtained. A comparison of the physical p ro perties and antibiotic activity of these compounds with those of corresponding erythromycin esters shows that erythromycin oxime and erythromycyl amine are very similar to erythromycin itself in their chemical and antimicrobial behaviour